biostudies-literatureChan PCharlie Teo FoundationAstellas Foundation for Research on Metabolic DisordersNINDS NIH HHSNCI NIH HHSthe NCIJapan Society for the Promotion of ScienceNINDS1772-1786https://www.ebi.ac.uk/biostudies/studies/S-EPMC12417823biostudies-literatureUnknown27(7)<h4>Background</h4>It has been reported that circadian clock components, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), are essential for glioblastoma (GBM) stem cell (GSC) biology and survival. Consequently, we developed a novel Cryptochrome (CRY) activator SHP1705, which inhibits BMAL1-CLOCK transcriptional activity.<h4>Methods</h4>We utilized GlioVis to determine which circadian genes are differentially expressed in non-tumor versus GBM tissues. We employed in vitro and in vivo methods to test the efficacy of SHP1705 against patient-derived GSCs and xenografts in comparison to earlier CRY activator scaffolds. We applied a novel REV-ERB agonist SR29065, which inhibits BMAL1 transcription, to determine whether targeting both negative limbs of theNeuro-oncologyAdvancing clinical response against glioblastoma: Evaluating SHP1705 CRY2 activator efficacy in preclinical models and safety in phase I trials.PMC12417823R01 CA238662F31 NS12065424H0055424H0226621H04766Mkhitaryan SHirota TKay SAKarapetyan GWu QRich JNSolt LAWang JCope JNagai YKamenecka TChan PMoats RAHovsepyan AfalseAdvancing clinical response against glioblastoma: Evaluating SHP1705 CRY2 activator efficacy in preclinical models and safety in phase I trials.<h4>Background</h4>It has been reported that circadian clock components, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), are essential for glioblastoma (GBM) stem cell (GSC) biology and survival. Consequently, we developed a novel Cryptochrome (CRY) activator SHP1705, which inhibits BMAL1-CLOCK transcriptional activity.<h4>Methods</h4>We utilized GlioVis to determine which circadian genes are differentially expressed in non-tumor versus GBM tissues. We employed in vitro and in vivo methods to test the efficacy of SHP1705 against patient-derived GSCs and xenografts in comparison to earlier CRY activator scaffolds. We applied a novel REV-ERB agonist SR29065, which inhibits BMAL1 transcription, to determine whether targeting both negative limbs of the2025-01-01T00:00:00Z2025 Sep2026-06-02T01:03:07.718Z2026-05-24T03:06:57.872ZS-EPMC124178234016811210.1093/neuonc/noaf089